Jack Henningfield/Pinney Associates Opinion

The following are the opinions of Jack E. Henningfield, Vice President for Research, Health Policy and Abuse Liability at Pinney Associates, and Adjunct Professor of Behavioral Biology at The Johns Hopkins University School of Medicine.1 Jack E. Henningfield has over 45 years of experience in his chosen field of research.

These opinions were compiled in conjunction with his colleagues at Pinney Associates, most notably, Edward Cone, Ph.D. and Reginald Fant, Ph.D

Kratom Overview

In brief, Mitragyna speciosa is a tropical deciduous tree within the coffee family (Rubiaceae) that is indigenous to Southeast Asia, particularly Thailand, Malaysia, Indonesia, Philippines, and Vietnam. Consumption of kratom is common in these Southeast Asia countries due to its abundance and effects regarded to be generally beneficial. In this region, kratom leaves are commonly chewed, used to make tea, or concentrated into an extract for addition to other beverages.2

Kratom contains several alkaloids with the most abundant alkaloid, mitragynine (MG), being 40 times less potent than the alkaloid 7α-hydroxy-7H-mitragynine (7-OH MG), of which the following highlighted manufactured product VivaZen contains zero 7-OH MG.

Consumption of kratom is common in these Southeast Asia countries due to its abundance and effects regarded to be generally beneficial.

In the U.S. kratom and its extracts have been used to provide relief of pain, counteract work-related fatigue, for fever reduction, diarrhea, coughing, hypertension, depression, and as a treatment for opiate withdrawal. Although dependence is reported, overdose, death and serious adverse events appear rare in Asia & the US, despite widespread use, and ready access to the natural plant material and various manufactured preparations.

Analysis of VivaZen Branded Drink

VivaZen which contains Mitragyna speciosa leaf extract, also known as kratom. The VivaZen formula is based on a specific traditional use of Mitragyna speciosa. Traditionally Southeast Asia laborers have used small quantities of kratom throughout the workday for the energizing and pain-relieving (minor aches and pains) effects. Kratom has been safely consumed as dietary supplement and folk remedy in Southeast Asia for centuries (Tanguay, 2011)3

VivaZen contains a standardized extract of kratom that is qualitatively and quantitatively similar in terms of the biologically-active alkaloid constituents of a single serve of the traditional kratom tea (but less than the average traditional daily consumption levels reported in the literature)

It is important to keep in mind that the primary active alkaloid in VivaZen is approximately 45 mg of MG. MG has been estimated to be approximately 3% bioavailable when taken by the oral route.

The safety of low doses of MG has also been evaluated in animal toxicology studies. Hassan and colleagues (2013)3 reviewed the data on the toxicology of MG as follows: In animal models, the toxicity of MG was claimed to be relatively low. Macko and colleagues (1972) found no evidence of toxicity, measured as tremors or convulsions, at doses as high as 920 mg/kg in dogs

Animal studies have demonstrated signs of physical dependence and withdrawal at what appear to be extraordinarily high dosages of MG, as compared to typical human use in the United States, and it is not clear that such doses could be practically achieved by consumption of a product such as Viva Zen.

Specifically, laboratory rats were given 30 mg/kg/day i.p., equating to an oral dose of about 990 mg/kg. Thus, to obtain equivalent doses of MG that produce physical dependence in the animal models, a 70kg human might need to consume 1,540 bottles per day, presumably for several weeks, at a cost of more than $10,000 per day.

Safety and toxicology of kratom and mitragynine.

Serious Adverse Events (SAE) were identified from the literature, by a review of the American Association of Poison Control Centers (AAPCC) Annual Reports (from 1999 through 2013), and by a FDA FOIA request initiated by a third party.

Globally fewer than 100 SAEs, primarily from Southeast Asia, have EVER been reported including kratom consumption. For perspective, it should be considered that kratom use is quite high in Southeast Asia, with likely over 1 million regular adult users in Thailand alone. A careful review of the case reports indicates that in most cases other causes, especially co-administered chemical substances or drugs, were likely responsible.5

Our main conclusions

Kratom, its extracts, and at least two alkaloids (MG and 7-OH MG) produce mixed pharmacological effects that are generally mild and stimulant-like at typical dosages. Consumption does not typically interfere with work or social activities and commitments, and in fact are widely reported in the U.S., as in Southeast Asia, to contribute to work productivity, quality of life, and social relationships.

MG and kratom have very low toxicity, and thus a favorable safety profile. To date, there have been no reports of fatal overdose from kratom per se.

It is plausible that VivaZen provides mild effects, including benefits, attributable to kratom and MG, however, its low total content of kratom extract and of MG in particular, would limit the strength of its benefits. Of course these same limitations would also limit its ability to cause dependence, withdrawal, and direct effects often considered as factors in substance abuse and dependence, namely, reinforcement, euphoria, and intoxication. These attributes of the product, along with its specific labeling concerning use, and maximally recommended use would be expected to contribute to consumption with low risk of dependence, abuse, and other undesirable and unintended effects.

Comparisons with other consumer products and dietary substances that meet criteria for at least mild potential for dependence and abuse.

Herbs that are commonly used and sometimes abused for energy bursts include guarana and kola nut, both of which contain caffeine.

Poppy seeds are harvested from the opium poppy and contain a mixture of opium alkaloids (e.g., morphine, codeine, thebaine). Poppy seeds are used as foodstuffs in many parts of the world. Depending upon the seed source, harvesting practices, and washing procedures, the content of opium alkaloids in poppy seed is widely variable. A serving of poppy seeds (e.g., poppy seed bagel) may contain a few micrograms to a few milligrams. Some foodstuffs contain larger amounts of poppy seeds (strudel prepared with poppy seeds). In the US, there have been reports of individuals who consumed these products, testing positive for morphine in workplace drug testing program. Due to the variable alkaloid content in poppy seeds, it is not possible to estimate what a standard serving of poppy seeds contains in terms of morphine content.

It should also be noted that there are a variety of other herbal and consumer products that likely have some reinforcing effects, but are not subject to regulation related to abuse or toxicity. For example, nutmeg contains myristicin, a natural compound that can produce hallucinogenic effects if taken in doses of around five teaspoons. When taking large amounts of nutmeg, it may take hours for auditory hallucinations to occur. This could result in increased overdose risk if the user thinks they haven’t taken enough.

Final Conclusion

There is an admittedly gray area represented, in my opinion, by kratom, caffeine, nicotine, over the counter cough, cold, and allergy medications, many herbals and spices, and quite frankly many prescription medications used to treat depression and other disorders, but which are not scheduled.

I believe that there should be clear evidence of actual or imminent public health harm, especially when there is also evidence of apparent consumer benefit before precautionary scheduling actions are taken. At this point, I do not believe precautionary scheduling is warranted for kratom products in general.

For VivaZen and like products, scheduling makes no more sense than would be the scheduling of hemp.